We will extend our investigations of the ileal and renal bile salt transport systems. These two systems function in the entero-hepatic circulation of bile salts and their biological economy, and were first described by this laboratory. The studies will include the following: a. the isolation and purification of macromolecules functioning in ileal transport from brush border membranes will be initiated. Evidence for assessing their transport function will be an assay system using reconstituted mixed liposome vesicles. b. our structure-activity studies have yielded information on the topography at the active site and has allowed us to design in a predicting manner, modified bile salt derivatives which can act as refractory substrates with inhibitory properties. We will continue these investigations to develop more effective reversible and irreversible inhibitors. The pharmacology of these inhibitors will then be assessed.